CA2911453A1 - Nouveaux composes et leurs compositions pharmaceutiques pour le traitement de la mucoviscidose. - Google Patents
Nouveaux composes et leurs compositions pharmaceutiques pour le traitement de la mucoviscidose.Info
- Publication number
- CA2911453A1 CA2911453A1 CA2911453A CA2911453A CA2911453A1 CA 2911453 A1 CA2911453 A1 CA 2911453A1 CA 2911453 A CA2911453 A CA 2911453A CA 2911453 A CA2911453 A CA 2911453A CA 2911453 A1 CA2911453 A1 CA 2911453A1
- Authority
- CA
- Canada
- Prior art keywords
- independently selected
- optionally substituted
- compound
- carboxamide
- groups
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 490
- 238000011282 treatment Methods 0.000 title claims abstract description 50
- 201000003883 Cystic fibrosis Diseases 0.000 title claims abstract description 41
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 36
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 232
- -1 bridged- Chemical group 0.000 claims description 216
- 125000000217 alkyl group Chemical group 0.000 claims description 201
- 125000005842 heteroatom Chemical group 0.000 claims description 194
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 190
- 150000003839 salts Chemical class 0.000 claims description 186
- 125000005843 halogen group Chemical group 0.000 claims description 124
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 112
- 229910052731 fluorine Inorganic materials 0.000 claims description 106
- 229910052801 chlorine Inorganic materials 0.000 claims description 103
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 90
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 84
- 125000002950 monocyclic group Chemical group 0.000 claims description 82
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 80
- 125000004076 pyridyl group Chemical group 0.000 claims description 56
- 229910052717 sulfur Inorganic materials 0.000 claims description 49
- 125000001072 heteroaryl group Chemical group 0.000 claims description 48
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 39
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 39
- 125000000335 thiazolyl group Chemical group 0.000 claims description 39
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 38
- 125000002883 imidazolyl group Chemical group 0.000 claims description 38
- 125000002971 oxazolyl group Chemical group 0.000 claims description 38
- 125000001544 thienyl group Chemical group 0.000 claims description 37
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 36
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 35
- 125000002541 furyl group Chemical group 0.000 claims description 34
- 229910052760 oxygen Inorganic materials 0.000 claims description 33
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 30
- 125000003386 piperidinyl group Chemical group 0.000 claims description 26
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 24
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 24
- 239000012453 solvate Substances 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 18
- 125000003003 spiro group Chemical group 0.000 claims description 18
- 125000006578 monocyclic heterocycloalkyl group Chemical group 0.000 claims description 17
- 125000001475 halogen functional group Chemical group 0.000 claims description 15
- 125000002393 azetidinyl group Chemical group 0.000 claims description 14
- 125000006580 bicyclic heterocycloalkyl group Chemical group 0.000 claims description 14
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 12
- 125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 12
- 125000002757 morpholinyl group Chemical group 0.000 claims description 12
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims description 11
- 125000005938 2,3-dihydro-1H-isoindolyl group Chemical group 0.000 claims description 11
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 10
- 238000000034 method Methods 0.000 abstract description 89
- 238000004519 manufacturing process Methods 0.000 abstract description 7
- DAUYIKBTMNZABP-UHFFFAOYSA-N thiophene-3-carboxamide Chemical compound NC(=O)C=1C=CSC=1 DAUYIKBTMNZABP-UHFFFAOYSA-N 0.000 description 231
- 239000000203 mixture Substances 0.000 description 180
- 125000003545 alkoxy group Chemical group 0.000 description 133
- 150000003857 carboxamides Chemical class 0.000 description 132
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 92
- 229910052739 hydrogen Inorganic materials 0.000 description 90
- 108010079245 Cystic Fibrosis Transmembrane Conductance Regulator Proteins 0.000 description 84
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 78
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 74
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 67
- 230000035772 mutation Effects 0.000 description 63
- 102100023419 Cystic fibrosis transmembrane conductance regulator Human genes 0.000 description 62
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 59
- 239000000243 solution Substances 0.000 description 58
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 56
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 54
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 51
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 48
- 239000000047 product Substances 0.000 description 43
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 43
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 42
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 36
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- 210000004027 cell Anatomy 0.000 description 35
- 229930192474 thiophene Natural products 0.000 description 35
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 34
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 32
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 31
- 238000005481 NMR spectroscopy Methods 0.000 description 31
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 31
- KOPFEFZSAMLEHK-UHFFFAOYSA-N 1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1C=CNN=1 KOPFEFZSAMLEHK-UHFFFAOYSA-N 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 30
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 30
- 238000003556 assay Methods 0.000 description 29
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 27
- 239000000543 intermediate Substances 0.000 description 27
- 230000000694 effects Effects 0.000 description 26
- 239000012074 organic phase Substances 0.000 description 25
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 24
- 235000017557 sodium bicarbonate Nutrition 0.000 description 24
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 24
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 23
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 23
- 201000010099 disease Diseases 0.000 description 23
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 22
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 22
- 238000004237 preparative chromatography Methods 0.000 description 22
- 239000002253 acid Substances 0.000 description 21
- 239000002904 solvent Substances 0.000 description 21
- 239000000725 suspension Substances 0.000 description 21
- 108091006146 Channels Proteins 0.000 description 20
- 102100026383 Vasopressin-neurophysin 2-copeptin Human genes 0.000 description 20
- 125000004432 carbon atom Chemical group C* 0.000 description 20
- 201000010064 diabetes insipidus Diseases 0.000 description 20
- 108091005957 yellow fluorescent proteins Proteins 0.000 description 20
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 19
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 19
- 108090000623 proteins and genes Proteins 0.000 description 19
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 19
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 18
- 239000007832 Na2SO4 Substances 0.000 description 18
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 18
- 229910052938 sodium sulfate Inorganic materials 0.000 description 18
- 235000011152 sodium sulphate Nutrition 0.000 description 18
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 17
- 235000019341 magnesium sulphate Nutrition 0.000 description 17
- 239000012528 membrane Substances 0.000 description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 17
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 16
- 230000004941 influx Effects 0.000 description 16
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 16
- BNYCHCAYYYRJSH-UHFFFAOYSA-N 1h-pyrazole-5-carboxamide Chemical compound NC(=O)C1=CC=NN1 BNYCHCAYYYRJSH-UHFFFAOYSA-N 0.000 description 15
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 15
- 230000032258 transport Effects 0.000 description 15
- 150000001408 amides Chemical class 0.000 description 14
- 125000003118 aryl group Chemical group 0.000 description 14
- 238000000746 purification Methods 0.000 description 14
- XQQBUAPQHNYYRS-UHFFFAOYSA-N 2-methylthiophene Chemical compound CC1=CC=CS1 XQQBUAPQHNYYRS-UHFFFAOYSA-N 0.000 description 13
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 13
- 238000004587 chromatography analysis Methods 0.000 description 13
- 229910052757 nitrogen Inorganic materials 0.000 description 13
- 235000018102 proteins Nutrition 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 13
- 239000000377 silicon dioxide Substances 0.000 description 13
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 13
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 description 12
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- 238000009472 formulation Methods 0.000 description 12
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 12
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 11
- 229910052799 carbon Inorganic materials 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- 150000002148 esters Chemical class 0.000 description 11
- 238000001704 evaporation Methods 0.000 description 11
- 230000008020 evaporation Effects 0.000 description 11
- 229910052740 iodine Inorganic materials 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 10
- 125000004193 piperazinyl group Chemical group 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- 102200128219 rs75527207 Human genes 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 10
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 10
- 239000003643 water by type Substances 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- 230000014509 gene expression Effects 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 238000002347 injection Methods 0.000 description 9
- 239000007924 injection Substances 0.000 description 9
- 229940002612 prodrug Drugs 0.000 description 9
- 239000000651 prodrug Substances 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 150000003568 thioethers Chemical class 0.000 description 9
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 8
- QKDCLUARMDUUKN-XMMPIXPASA-N 6-ethyl-3-[4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino]-5-[(3r)-1-prop-2-enoylpyrrolidin-3-yl]oxypyrazine-2-carboxamide Chemical compound N1=C(O[C@H]2CN(CC2)C(=O)C=C)C(CC)=NC(C(N)=O)=C1NC(C=C1)=CC=C1N(CC1)CCC1N1CCN(C)CC1 QKDCLUARMDUUKN-XMMPIXPASA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 102000012605 Cystic Fibrosis Transmembrane Conductance Regulator Human genes 0.000 description 8
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 8
- 239000007836 KH2PO4 Substances 0.000 description 8
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 8
- 125000002619 bicyclic group Chemical group 0.000 description 8
- 230000002950 deficient Effects 0.000 description 8
- 238000010511 deprotection reaction Methods 0.000 description 8
- 239000008103 glucose Substances 0.000 description 8
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 8
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 8
- 235000019796 monopotassium phosphate Nutrition 0.000 description 8
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 8
- 229910052700 potassium Inorganic materials 0.000 description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 description 8
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 229940124597 therapeutic agent Drugs 0.000 description 8
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 7
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 150000001450 anions Chemical class 0.000 description 7
- 125000004429 atom Chemical group 0.000 description 7
- 210000000170 cell membrane Anatomy 0.000 description 7
- 238000010438 heat treatment Methods 0.000 description 7
- 239000002953 phosphate buffered saline Substances 0.000 description 7
- 235000015320 potassium carbonate Nutrition 0.000 description 7
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 7
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 7
- 150000003573 thiols Chemical class 0.000 description 7
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 6
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- SUZLHDUTVMZSEV-UHFFFAOYSA-N Deoxycoleonol Natural products C12C(=O)CC(C)(C=C)OC2(C)C(OC(=O)C)C(O)C2C1(C)C(O)CCC2(C)C SUZLHDUTVMZSEV-UHFFFAOYSA-N 0.000 description 6
- 206010012735 Diarrhoea Diseases 0.000 description 6
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 6
- 208000003556 Dry Eye Syndromes Diseases 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- 101100348848 Mus musculus Notch4 gene Proteins 0.000 description 6
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 229910000024 caesium carbonate Inorganic materials 0.000 description 6
- OHCQJHSOBUTRHG-UHFFFAOYSA-N colforsin Natural products OC12C(=O)CC(C)(C=C)OC1(C)C(OC(=O)C)C(O)C1C2(C)C(O)CCC1(C)C OHCQJHSOBUTRHG-UHFFFAOYSA-N 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 230000007547 defect Effects 0.000 description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
- 210000000981 epithelium Anatomy 0.000 description 6
- 230000000155 isotopic effect Effects 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 125000005961 oxazepanyl group Chemical group 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 102200132105 rs193922525 Human genes 0.000 description 6
- 102200128599 rs80282562 Human genes 0.000 description 6
- 239000002002 slurry Substances 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 5
- 239000007821 HATU Substances 0.000 description 5
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 5
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 5
- LBCYNYXWCQQSAL-UHFFFAOYSA-N S(=O)(=O)=NC(=O)C1=CSC=C1 Chemical compound S(=O)(=O)=NC(=O)C1=CSC=C1 LBCYNYXWCQQSAL-UHFFFAOYSA-N 0.000 description 5
- 208000021386 Sjogren Syndrome Diseases 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 125000005605 benzo group Chemical group 0.000 description 5
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- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
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CA3122383A CA3122383A1 (fr) | 2013-05-07 | 2014-05-06 | Nouveaux composes et leurs compositions pharmaceutiques pour le traitement de la mucoviscidose. |
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GB201308137A GB201308137D0 (en) | 2013-05-07 | 2013-05-07 | Novel compounds and pharmaceutical compositions thereof for the treatment of cystic fibrosis |
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GB201317932A GB201317932D0 (en) | 2013-10-10 | 2013-10-10 | Novel compounds and pharmaceutical compositions thereof for the treatment of cystic fibrosis |
GB13179320 | 2013-10-10 | ||
PCT/EP2014/001202 WO2014180562A1 (fr) | 2013-05-07 | 2014-05-06 | Nouveaux composés et leurs compositions pharmaceutiques pour le traitement de la mucoviscidose |
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CA2911453A Active CA2911453C (fr) | 2013-05-07 | 2014-05-06 | Nouveaux composes et leurs compositions pharmaceutiques pour le traitement de la mucoviscidose. |
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US (2) | US9382254B2 (fr) |
EP (1) | EP2994463B1 (fr) |
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CA (2) | CA3122383A1 (fr) |
LU (1) | LU92578B1 (fr) |
MX (1) | MX368263B (fr) |
WO (1) | WO2014180562A1 (fr) |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8563573B2 (en) | 2007-11-02 | 2013-10-22 | Vertex Pharmaceuticals Incorporated | Azaindole derivatives as CFTR modulators |
US8802868B2 (en) | 2010-03-25 | 2014-08-12 | Vertex Pharmaceuticals Incorporated | Solid forms of (R)-1(2,2-difluorobenzo[D][1,3]dioxo1-5-yl)-N-(1-(2,3-dihydroxypropyl-6-fluoro-2-(1-hydroxy-2-methylpropan2-yl)-1H-Indol-5-yl)-Cyclopropanecarboxamide |
EP3045452A1 (fr) | 2010-04-22 | 2016-07-20 | Vertex Pharmaceuticals Inc. | Procédé de production de composés cycloalkyle-carboxamide-indole |
HUE062736T2 (hu) | 2014-04-15 | 2023-12-28 | Vertex Pharma | Gyógyszerészeti készítmények cisztás fibrózis transzmembrán konduktancia regulátor által mediált betegségek kezelésére |
CA2952862A1 (fr) | 2014-06-19 | 2015-12-23 | Proteostasis Therapeutics, Inc. | Composes, compositions et procedes pour augmenter l'activite du cftr |
AU2015279047B2 (en) | 2014-06-27 | 2020-01-02 | Nogra Pharma Limited | Aryl receptor modulators and methods of making and using the same |
SI3203840T1 (sl) | 2014-10-06 | 2020-10-30 | Vertex Pharmaceuticals Incorporated | Modulatorji regulatorja transmembranske prevodnosti pri cistični fibrozi |
US10392378B2 (en) | 2014-12-23 | 2019-08-27 | Proteostasis Therapeutics, Inc. | Derivatives of 5-phenyl- or 5-heteroarylathiazol-2-carboxylic amide useful for the treatment of inter alia cystic fibrosis |
MA41253A (fr) | 2014-12-23 | 2017-10-31 | Proteostasis Therapeutics Inc | Composés, compositions et procédés pour augmenter l'activité du cftr |
WO2016105468A1 (fr) | 2014-12-23 | 2016-06-30 | Proteostasis Therapeutics, Inc. | Dérivés de 3-hétéroarylisoxazol-5-amide carboxylique utiles dans le traitement, entre autres, d'une fibrose kystique |
CA2988046A1 (fr) | 2015-06-02 | 2016-12-08 | Abbvie S.A.R.L. | Pyridines substituees et methode d'utilisation |
US9840513B2 (en) | 2015-07-16 | 2017-12-12 | Abbvie S.Á.R.L. | Substituted tricyclics and method of use |
US10548878B2 (en) * | 2015-07-24 | 2020-02-04 | Proteostasis Therapeutics, Inc. | Compounds, compositions, and methods of increasing CFTR activity |
BR112018007145A2 (pt) | 2015-10-09 | 2018-11-06 | AbbVie S.à.r.l. | ácidos pirazolo[3,4-b]piridin-6-carboxílicos substituídos e o seu uso |
CA3000802A1 (fr) | 2015-10-09 | 2017-04-13 | Abbvie S.A.R.L. | Nouveaux composes destines au traitement de la fibrose kystique |
KR20180083323A (ko) | 2015-10-09 | 2018-07-20 | 애브비 에스.에이.알.엘. | N-설포닐화 피라졸로[3,4-b]피리딘-6-카복스아미드 및 사용 방법 |
AU2017240685B2 (en) | 2016-03-31 | 2021-08-12 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator |
BR112018070747B1 (pt) | 2016-04-07 | 2024-01-09 | Proteostasis Therapeutics, Inc | Átomos de silicone contendo análogos de ivacaftor, composições farmacêuticas e usos terapêuticos |
CN109219602A (zh) | 2016-04-26 | 2019-01-15 | 艾伯维公司 | 囊性纤维化跨膜传导调节物蛋白的调节剂 |
US10138227B2 (en) | 2016-06-03 | 2018-11-27 | Abbvie S.Á.R.L. | Heteroaryl substituted pyridines and methods of use |
AU2017280206A1 (en) | 2016-06-21 | 2019-01-17 | Proteostasis Therapeutics, Inc. | Compounds, compositions, and methods for increasing CFTR activity |
WO2018064632A1 (fr) | 2016-09-30 | 2018-04-05 | Vertex Pharmaceuticals Incorporated | Modulateur de régulateur de conductance transmembranaire de fibrose kystique, compositions pharmaceutiques, procédés de traitement et procédé de fabrication du modulateur |
US9981910B2 (en) | 2016-10-07 | 2018-05-29 | Abbvie S.Á.R.L. | Substituted pyrrolidines and methods of use |
US10399940B2 (en) | 2016-10-07 | 2019-09-03 | Abbvie S.Á.R.L. | Substituted pyrrolidines and methods of use |
CN106496080B (zh) * | 2016-10-19 | 2019-01-15 | 广东工业大学 | 一种巯基功能化芳基羧酸的制备方法 |
US20190256474A1 (en) | 2016-10-26 | 2019-08-22 | Proteostasis Therapeutics, Inc. | N-phenyl-2-(3-phenyl-6-oxo-1,6-dihydropyridazin-1-yl)acetamide derivatives for treating cystic fibrosis |
WO2018081381A1 (fr) | 2016-10-26 | 2018-05-03 | Proteostasis Therapeutics, Inc | Composés de pyridazine, compositions et méthodes permettant de moduler cftr |
EP3532469A1 (fr) | 2016-10-26 | 2019-09-04 | Proteostasis Therapeutics, Inc. | Composés, compositions et méthodes permettant de moduler cftr |
MX2019006637A (es) | 2016-12-09 | 2019-08-21 | Vertex Pharma | Modulador del regulador de conductancia transmembrana de fibrosis quistica composiciones farmaceuticas metodos de tratamiento y proceso para producir el modulador. |
WO2018116185A1 (fr) | 2016-12-20 | 2018-06-28 | AbbVie S.à.r.l. | Modulateurs cftr deutérés et procédés d'utilisation |
TW201831471A (zh) | 2017-02-24 | 2018-09-01 | 盧森堡商艾伯維公司 | 囊腫纖化症跨膜傳導調節蛋白的調節劑及其使用方法 |
EP3615528B1 (fr) | 2017-04-28 | 2022-02-16 | Proteostasis Therapeutics, Inc. | Dérivés 4-sulfonylaminocarbonylquinoline pour augmenter l'activité cftr |
AU2018279646B2 (en) | 2017-06-08 | 2023-04-06 | Vertex Pharmaceuticals Incorporated | Methods of treatment for cystic fibrosis |
EP3654969A1 (fr) | 2017-07-17 | 2020-05-27 | Vertex Pharmaceuticals Incorporated | Méthodes de traitement de la fibrose kystique |
JP7121794B2 (ja) | 2017-08-02 | 2022-08-18 | バーテックス ファーマシューティカルズ インコーポレイテッド | ピロリジン化合物を調製するためのプロセス |
US10988454B2 (en) | 2017-09-14 | 2021-04-27 | Abbvie Overseas S.À.R.L. | Modulators of the cystic fibrosis transmembrane conductance regulator protein and methods of use |
WO2019071078A1 (fr) | 2017-10-06 | 2019-04-11 | Proteostasis Therapeutics, Inc. | Composés, compositions et méthodes pour augmenter l'activité de cftr |
AU2018351533B2 (en) | 2017-10-19 | 2023-02-02 | Vertex Pharmaceuticals Incorporated | Crystalline forms and compositions of CFTR modulators |
MX2020005753A (es) | 2017-12-08 | 2020-08-20 | Vertex Pharma | Procesos para producir moduladores de regulador de conductancia transmembranal de fibrosis quistica. |
US20190210973A1 (en) | 2018-01-05 | 2019-07-11 | The Curators Of The University Of Missouri | Compounds and methods for treatment of cystic fibrosis |
TWI810243B (zh) | 2018-02-05 | 2023-08-01 | 美商維泰克斯製藥公司 | 用於治療囊腫纖化症之醫藥組合物 |
WO2019193062A1 (fr) | 2018-04-03 | 2019-10-10 | Abbvie S.Á.R.L | Pyrrolidines substituées et leur utilisation |
WO2019200246A1 (fr) | 2018-04-13 | 2019-10-17 | Alexander Russell Abela | Modulateurs du régulateur de la conductance transmembranaire de la fibrose kystique, compositions pharmaceutiques, procédés de traitement et procédé de fabrication du modulateur |
JP7187819B2 (ja) * | 2018-05-22 | 2022-12-13 | Jnc株式会社 | 液晶性化合物、液晶組成物および液晶表示素子 |
EP3747882A1 (fr) | 2019-06-03 | 2020-12-09 | AbbVie Overseas S.à r.l. | Modulateurs de promédicament de la protéine régulatrice de la conductance transmembranaire de la fibrose kystique et procédés d'utilisation |
WO2021011327A1 (fr) | 2019-07-12 | 2021-01-21 | Orphomed, Inc. | Composé pour le traitement de la fibrose kystique |
BR112022009202A2 (pt) | 2019-11-12 | 2022-09-06 | Genzyme Corp | Heteroarilaminosulfonamidas de 6 membros para tratamento de doenças e condições mediadas por atividade deficiente de cftr |
WO2021113809A1 (fr) | 2019-12-05 | 2021-06-10 | Genzyme Corporation | Arylamides et leurs procédés d'utilisation |
WO2021113806A1 (fr) | 2019-12-05 | 2021-06-10 | Genzyme Corporation | Arylamides et leurs procédés d'utilisation |
EP4274828A1 (fr) | 2021-01-06 | 2023-11-15 | AbbVie Global Enterprises Ltd. | Modulateurs de la protéine régulatrice de la conductance transmembranaire fibrokystique et méthodes d'utilisation |
US20220213041A1 (en) | 2021-01-06 | 2022-07-07 | AbbVie Global Enterprises Ltd. | Modulators of the Cystic Fibrosis Transmembrane Conductance Regulator Protein and Methods of Use |
CA3230259A1 (fr) | 2021-09-03 | 2023-03-09 | Junkai Liao | Composes indoles et procedes d'utilisation |
EP4396176A1 (fr) | 2021-09-03 | 2024-07-10 | Genzyme Corporation | Composés indoles et leurs utilisations dans le traitement de la fibrose kystique |
GB202117127D0 (en) * | 2021-11-26 | 2022-01-12 | Epidarex Exeed Ltd | Compounds |
WO2024054851A1 (fr) | 2022-09-07 | 2024-03-14 | Sionna Therapeutics | Composés macrocycliques, compositions et méthodes d'utilisation associées |
WO2024054845A1 (fr) | 2022-09-07 | 2024-03-14 | Sionna Therapeutics | Composés macrocycliques, compositions et leurs procédés d'utilisation |
WO2024054840A1 (fr) | 2022-09-07 | 2024-03-14 | Sionna Therapeutics | Composés macrocycliques, compositions et procédés d'utilisation associés |
CN117417293B (zh) * | 2023-12-18 | 2024-03-19 | 齐鲁晟华制药有限公司 | 一种氟吡菌酰胺的合成方法 |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP3409029B2 (ja) * | 1997-10-03 | 2003-05-19 | メルク フロスト カナダ アンド カンパニー | Pdeiv阻害剤としてのアリールチオフェン誘導体 |
US20060293307A1 (en) | 2002-07-29 | 2006-12-28 | Anita Mehta | Oxazolidinone derivatives as antimicrobials |
US7696244B2 (en) * | 2003-05-16 | 2010-04-13 | The Regents Of The University Of California | Compounds having activity in increasing ion transport by mutant-CFTR and uses thereof |
DE602004022819D1 (de) * | 2003-06-06 | 2009-10-08 | Vertex Pharma | Von atp-bindende kassette transportern |
JP2005097276A (ja) * | 2003-08-22 | 2005-04-14 | Takeda Chem Ind Ltd | 縮合ピリミジン誘導体およびその用途 |
AU2005210474B2 (en) * | 2004-01-30 | 2011-07-07 | Vertex Pharmaceuticals Incorporated | Modulators of ATP-Binding cassette transporters |
US20070010537A1 (en) * | 2004-08-20 | 2007-01-11 | Kazumasa Hamamura | Fused pyramidine derivative and use thereof |
WO2007013975A2 (fr) | 2005-07-20 | 2007-02-01 | Pharmorx Inc. | Compositions et procedes destines a controler l'abus de medicaments |
US7868177B2 (en) | 2006-02-24 | 2011-01-11 | Amgen Inc. | Multi-cyclic compounds and method of use |
EP2019826B1 (fr) * | 2006-05-23 | 2012-08-29 | Vertex Pharmaceuticals, Inc. | Thiophène-carboxamides inhibiteurs des protéines kinases |
KR20100124778A (ko) | 2008-02-25 | 2010-11-29 | 메르크 파텐트 게엠베하 | 글루코키나제 활성제들 |
GB0813873D0 (en) | 2008-07-30 | 2008-09-03 | Univ Dundee | Compounds |
EP2421528A4 (fr) * | 2009-04-20 | 2012-10-17 | Inst Oneworld Health | Composés, compositions et méthodes comprenant des dérivés du 1,3,4-oxadiazole |
SA114350273B1 (ar) | 2009-04-21 | 2016-06-23 | امونولايت، ال ال سي | أنظمة وطرق غير انتشارية للتحويل العلوي للطاقة للتعديل الحيوي الضوئي في الموقع |
CN104428282B (zh) | 2012-07-12 | 2017-10-20 | 日产化学工业株式会社 | 肟取代酰胺化合物和有害生物防除剂 |
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LU92578B1 (fr) | 2014-12-15 |
US9867806B2 (en) | 2018-01-16 |
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CA2911453C (fr) | 2021-08-03 |
CA3122383A1 (fr) | 2014-11-13 |
WO2014180562A1 (fr) | 2014-11-13 |
AU2014264936B2 (en) | 2018-09-27 |
JP2019112449A (ja) | 2019-07-11 |
CN105531268A (zh) | 2016-04-27 |
US20160263084A1 (en) | 2016-09-15 |
EP2994463B1 (fr) | 2017-10-25 |
US9382254B2 (en) | 2016-07-05 |
BR112015027964A2 (pt) | 2017-09-05 |
BR112015027964B1 (pt) | 2023-01-10 |
CN105531268B (zh) | 2017-09-12 |
MX2015015412A (es) | 2016-06-10 |
EP2994463A1 (fr) | 2016-03-16 |
JP2016517895A (ja) | 2016-06-20 |
AU2014264936A1 (en) | 2015-11-19 |
MX368263B (es) | 2019-09-26 |
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